Chaper 8 Flashcards
(160 cards)
1
Q
Which anatomical sites do naive TC encounter antigen
A
At the start of the primary immune response
In a secondar lymphoid node
2
Q
Why are dendritic cells more efficient than macrophages?
A
DC are migratory and transport antigen to neighboring secondary lymphoid tissue
3
Q
Which selectin has a role in circulation of TC b/w blood and lymphoid tissues
A
L-selectin binds to carbs in hEV
3 types :
GLYCSM-1
CD34
4
Q
3 classes of effector TC
A
Cytotoxic TC
Th1
TH2
5
Q
TC activation= TCA is what?
A
Referred to as the priming an is the first stage of a primary adaptive immune response
6
Q
What are the events of T-lymphocyte Imm?
A
Priming of naive TC
Activation of TC
Response of activated T helper and T cytotoxic
7
Q
Printing of naive TC is analogous to?
A
what of BC activation by FDC
8
Q
What does dendritic cells link?
A
Innate and adaptive imm sys.
9
Q
What is priming most often initiated by?
A
Dendritic cells
10
Q
Where do dendritic cells reside?
A
In the epithelial cells
Langerhand cells - spec in the skin
11
Q
Where for priming occur at?
A
Lymph node the nearest one
2nd tissue
12
Q
How does the dendritic cell work?
A
Engulfs -bac,virus,proteins etc
Does antigen capture
13
Q
What is antigen capture?
A
AC is what dendritic cells do they
- phagocytosis
- recept mediated endocytosis
- macro-pintocytosis
14
Q
What is the major function of DC?
A
Trigger TC response
15
Q
What mcH does DC express?
A
Both!
16
Q
What receptors do DC have?
A
Mannose
TLR
17
Q
What does AC lead to?
A
Maturation into APC
18
Q
Activation of DC means what additional?
A
Pro inflam cytokines
- TNF
- IL-1
19
Q
DC activation causes….
A
No longer able I further engulf more antigens
20
Q
Activation of DC does…
A
Increase mHc II
Migration of lymph node expresses ccr7
Cytokines receptor
21
Q
Activation of DC summary
A
Pro inflamm cytokines
-TNF, IL-1
No longer engulf role has changed to priming
Increase MHC II
Migration of LN
- expression of CCR7
- cytokines receptor for CCL21 made in 2LN
22
Q
How does the naive TC enter LN?
A
Via afferent lymph vessel
From bv pass through HEV
23
Q
What chemokine attracts naive TC into LN?
A
CCL18- secreted by DC
24
Q
Function of CCL18
A
Gets naive to the right place
25
What does CCL19&21 function?
Cause the DC leave the draining lymph and enter draining lymph
26
What chemokine a are secreted by stromal cells and DC?
CCL21&19
27
What is the receptor that binds to CCL21&19?
CCR7
28
CCL21& 19 are bound to what?
HEV where they establish a concentration grad along the endothelial surface
29
What are the Homing cytokines in the LN ?
CCL21&19
In the LN cortex
30
Homing of TC to LN adhesion molecules are what?
TC =L-selectin
31
HEV adhesion molecules
CD34 & GlyCAM-1
32
Adhesion molecules cause what to happen to the TC?
Causes the naive TC to slow down & attach to the HEV
33
What is apart of the afferent lymphatics?
Mature DC can't home through blood
Up regulated CCR7 in response to inflammation
34
Who does LFA-1 strength hold to?
ICAM
35
What are the steps of homing TC to LN?
1. The binding of L-selectin to slow naive TC down
2. The binding of CCR7: CCR19 or 21
3. Tight adhesion between LFA-1 and ICAM-1
4. Diapedesis- lymphocytes leaves blood and enters LN
36
What is on the DC?
lFA-1 & ICAM-1
37
What happens if the TC encounters matching antigen?
Intracellular signaling
Weak binding - strong binding lFA-1 binds tightly to ICAm-1
Then the TC remains in LN attached to DC to becomes primed"
38
What type of change does the TCR send to LFA-1?
Conformational change to increase the affinity and prolongs the cell-cell contact
39
What happens then of TC does not meet antigen
TC dissociates from DC - no strong binding
It leaves via efferent vessel to keep searching
Because naive TC can. Survive for years
Will still undergo occasional replication
40
What are the two signals that are needed for priming events?
TCR-peptide/ CD-MHC
Co stimu by B7 (only on DC )
41
What does B7 express and bind to?
Expressed by only APC
Initiation by infection
B7 binds to CD28 on naive TC
42
What do the two activations signals for priming to occur do?
TC prolifer and activation
| Need both to happen at the same time on same cell
43
Recap of receptors
What's on CD4 helper T ?
```
CD4
TCR
CD3
Zeta
CD28
LFA-1
```
44
What is CD 4?
Signal transduction
45
What Is TCR ?
Antigen recognition
46
What are the signal transduction molecules?
CD3
Zeta
CD28
47
What is the adhesion molecule on CD4?
LFA-1
48
What's is expressed on MHC II?
B7
| ICAM-1
49
What binds to what?
| CD4 helper T lymphocytes binds to ligand in mHc expressing APC
TCR-MHC II
CD28-B7
LFA-1 to iCAM-1
50
Name the 3 types of APC
DC
Macrophages
BC
51
Where are macrophages located?
Cortex and medulla
They hang out where they are
They prevent systemic infection
Can present to TC in the peripheral tissue only in the LN
52
What types of cells do macrophages present peptides to ?
Already primed TC
53
What do macrophages present in the presence of infecTion?
They induce B7 a co stimulation needed for TC proliferation
54
If the macrophage is outside the 2nd lymph will it activate TC?
No! Only in LN it will
55
Where is DC found?
Only in cortical TC area
56
macro an DC come from what?
The same lineage
57
BC is what type of effectiveness of an APC?
The least !
Does not express co-stim
Needs to be activated by TC
Present via mHc II
58
Order of APC
DC>Macro>BC
59
What initiates TC synapse ?
Clustering
60
Where is the signal transmitted for the TC synapse?
Interior
61
What is associated with TC -S?
ITAMs - ass with CD3
| ZAP-70 : ass with protein kinase
62
What is the sequence of the signaling in TC?
```
Bindin of mhC-TCr
Phosphor of ITAMs
Co Recp binds
Binding of zap 70 to zeta CD3
Zap70 phosphor by LCK
```
63
Wht is LCK ?
A signal transduction molecule
64
If a def in zap70?
Normal TC #
Unresponsive TC
SCID
We lose transcription factor
65
Def in zap70
Unable to develop intracellular signals in engagement of their antigen receptor
66
What are the ultimate TF of downstream signaling pathways?
NF-kb
NFAT
AP-1
67
Downstream signaling pathway means what ?
TF
TC proliferation
IL-2 production
68
What is IL-2 ?
Secreted by activated TV
69
What does IL-2 bind to?
IL-2 receptor in TC autocrine
| That drives clonal expanison
70
Why does IL-2 drive ?
Clonal expanison
71
What does IL 2 require ?
Signals via TCR complex - activation of NFAT
Co-stim signals
- TF to increase transcription of IL2 gene
72
IL 2 receptor have?
B and gamma
73
What does IL 2 receptor synthesis ?
Alpha chain
| High affinity of Il-2 receptor
74
Hat does the IL2 receptor stimulate?
TC to enter cell cycle =proliferation
75
What is the important result of priming?
Expression of IL-2 receptor on surface
Secretion if IL-2
=activation
76
What happens when IL-2 binds to the IL-2 receptor?
TC stimulates itself
TC rep expansion of primed TC
Now ready to respond to re MHC peptide
77
What happens is there is no co stim for TC proliferation?
The cell because anergy= floats around can't respond
Can't make IL-2
78
After the TC is primed why doesn't the TC respond immediately?
B/c don't want the DC to be destroyed by the t-cytoxic cell
79
Why after priming is CTLA-4 expressed?
It dampens down activation and limits cell proliferation= down regulation
80
What is CTLA4 structurally similar to?
CD28
81
What does CTLA 4 bind to?
Any remaining B7
82
Again what is the purpose of CTLA after priming?
Inhibits co-stimulation
Not letting the TC get too strong
83
What does CTLA4 stand for?
Cytotoxic T lymphocyte antigen 4
84
What is CTLA 4 an alternative ligand for?
B7 because CTLA has a higher affinity
85
Why is priming important?
Because if unprimed TC encounters MHC peptide wo co-stimulation
86
Why is priming necessary?
No priming can occur if TC binds to self peptide wo B7
If primed wo B7 =anergic
Autoimmunity may be inhibited
87
What does l-selec bind to ?
GlyCAM-1
Slows down rolling
88
What does CCL21 bind to?
CCR7
| Chemo attractant drawing into the homing
89
LFA-1 on the TC binds to what?
ICAM-1 on APC
Tight adhesion stops the rolling
90
CD28 is on what binds to what on what...?
Cd28 on TC
Binds to B7 on APC
91
If a cell has the b7 and CD28 but is present on other self cell what which this cell have?
No effect
92
If a cell complex has cd28 but no b7 what effect will this have?
No co stim =anergy
93
What are CD4 Called?
Helper TC
| Reg TC
94
What types of helper TC are there ?
1= cell mediated
2= humoral
And Th17
95
What is TH1 function ?
Type II INTERFERON
TNF
Cytotoxic TC, macrophages
96
Why are Th2 cells?
IL4
IL6
BC activation
97
What does IL4 do?
A type of Th2
| And function to isotype switching to IgE
98
What creates Treg cell?
TGF-B
99
What secreted TH1?
IL-12
| IFN-gamma
100
What cytokines induced TH2?
IL-4
101
What is does a Treg cell express?
Foxp3
TGF-B
IL-10
102
What does TH1 have?
TBET
IL-2
INF-gamma
103
What does TH2 cell have?
GATA- 3
IL4
IL5
104
What does the most adaptive imm respon contrib?
From both TH 1&2
105
Leprosy if bias to TH1 ....?
Macro suppresses bacterial growth
Slow disease progression
Pt survival
106
Leprosy bias towards TH2?
Inaccessible to antibody
Widespread
Fatal
107
Th1 has what type of clinical sig?
Type 1 diabetes
Specific for peptides in pancreas
Overstim macro
108
Other helper TC ?
Th17
109
What does Th17 secret ?
Il-17
110
What is Th17 important with?
Inflammation
- recruit of neutrophils
- secretion of defensins
- implicated for autoimmune disorders
111
Where is Th17 found at?
Interfaces of external environment and internal enir
112
Where else is Th17 found at?
Bacterial and fungal infections
113
What is the naive cd8 cell activated by?
On DC
114
Which has the stronger co stim activity ?
CD8
115
How is naive cd8 activated?
3 ways
Virus infec DC
Two ways that APC offer co stim
- Help from cd4 cytokines induce B7
- cd4 cytokines ex IL-2 act directly in CD8
116
Summary of activation of CD
Virus DC express B7
CD4 activates APC expressing B7
CD4 secretes IL-2 then binds to CD8
117
What effector cells leave the 2 lymphoid?
CD8
CD4
TH1
118
What effector cells remain in secondary lymphoid?
CD4
| TH2- bcuz import for BC and BC are found in 2 lymph
119
Why is relaxation good for maturation into effector cells?
Host cells son have B7 want relaxed the cd8 cell can respond to antigen wo co stim
120
Alternation of cell surface marker is what?
LFA-1
121
LFA -1 does what?
Mediates cell migration and interaction with Apc
122
What is Cd2
Cell adhesion molecule
Binds to Cd2R
Mature TC
No BC
123
CD2 receptor is what?
LFA-3
124
What does CD2 bind to?
What is the function of CD2?
To LFA 3 on APC
Enables TC to response to lower concentrations of antigens
Mediated adhesion between TC and APC
Induces TC cytokines produc
125
What is VLA -4?
An integrin that allows effector TC to move into inflamed tissue
126
Effector TC excludes what?
LN = no L-selectin
127
What does the alt of cel surface marker do ?
Decrease L-selec
128
Effector TC function is Carried out by what?
Cytokines
Cytotoxins
129
What do cytokines do ?
Alter behavior of targets cells
Autocrine paracrine agents
130
Why do cytotoxins do?
Used to kill infected cells
CTL
131
CTL
Belong to CD8
A:b TCR
Recog MHC I
Most dies or become memory
132
What MHC does cTL belong to ?
MHC I
133
CTL effector response?
Sacrifice host cell to prevent infection
134
CTL effector Resp
Path inaccessible to antibodies an soluble proteins
135
What does CTL contain ?
Lyric granules
136
Types of CTL lytic granules?
Mod lysosomes
| Contain cytotoxins!!!
137
What are cd8?
Selective killers of target cells
138
What is the process of killing for CD8?
Need TCR
- MTOC center
- GA=Golgi
Release cytotoxins
CTL makes new granules
139
Cytotoxic TC kill TC by what?
Apop
140
How does apop occur from cytotoxic TC
Release cytoxins
| Fas ligand
141
More in cytotoxins they contain what?
Granzymes
| Perforins
142
Wht are granzymes?
Act apop
| Create ROS
143
Perforin does what?
Creates pores for delievery
144
What does fas -L expressed by
CTL express death activator
145
What does Fas do?
Activates caspases
Apop
146
Other func of CtL
InF- gamma activates macrophages
147
Lymphotoxins are what ?
Induces adhesion on endothelial cell allowing phagocytic cell to bind
148
If pathogens live in macrophages then it is not presented by what mHC?
No MHC I
| Therefore infect is fought by TH1 and CD4
149
What is macrophage activation?
Alternation that enables the activated macro to perform function that can be performed by resting macro
150
What are the two signals for macrophage activation?
Interferon gamma
Binding of CD40
151
What is interferon gamma express?
CD40
152
What is IFN- gamma produced by?
CD8 and TH1
153
What does CD8 not produced ?
CD40
154
What else has IFN-gamma?
NK cells
155
TH2 activated BC cytokines?
IL4
5
6
156
Where is the follicular B helper TC func ?
Germinal center
157
What does CD40 & CD40L help?
Interaction between TC & BC
158
What is diff between TFH and TH2?
TFH distinct homing in 2nd Lymph
159
NK cells
```
TC
A:b TCR
Glycolipid antigens
Secrete cytokines
IFN-gamma
IL-4
```
160
NK is a link bw what?
Adaptive and innate imm
